With the genome project going forward, there has been an active move afoot to grasp a living organism at the DNA or protein level for examination for disease or understanding of the phenomena of life. To examine the status of gene expression is effective for the understanding of the phenomena of life or the investigation of the workings of genes. A probe array, namely, a DNA chip or a protein chip, having many DNA probes or protein probes partitioned according to the type of probe and immobilized on the surface of a solid body such as slide glass, has come into use as an effective method for examination of the status of gene expression. Chip making methods include a method that involves synthesizing a designed sequence of oligomers, base by base, with many compartmented cells, using photochemical reaction and lithography that is widely used in the semiconductor industry (Science 251, 767-773 (1991)), and a method that involves implanting plural types of probes, one by one, in compartments (Science 270, 467-470 (1995); and Nat. Biotechnol. 18, 438-441 (2000)).
With any of these methods, the fabrication of the chip requires the immobilization of the DNA probes or the protein probes on each array, or the base-by-base synthesis of the oligomers if specialized for the DNA probes; hence the fabrication takes time and effort, resulting in high costs. Also, the probes are generally mounted as liquid droplets on the surface of the solid body, which in turn involves problems in that there is compartment-to-compartment variation, that it is not easy to make varying combinations of the types of probes, and that manipulation is not easy for a user, and so on.
To solve the above problems, there has been a proposal of a probe array, namely, a particle array, having a collection of plural types of particles, which are prepared by immobilizing the DNA probes or the protein probes on the particles (Clinical Chemistry 43, 1749-1756 (1997); Nucleic Acids Research 30, e87 (2002); and Description in U.S. Pat. No. 6,023,540). The advantage of the probe array using the particles is that the probe array can be fabricated without particle-to-particle variation in probe density since a probe immobilization method utilizing chemical reaction in a solution can be employed.
For the DNA chip or the protein chip, a method that involves identifying the type of probe by any one of the point of oligomer formation and the point of probe spot is adopted. Meanwhile, for the probe array using the particles having the probes immobilized thereon, any one of a method using a color-coded particle for each probe (Clinical Chemistry 43, 1749-1756 (1997); and Description in U.S. Pat. No. 6,023,540) and a method that involves identifying the type of probe by the sequence in which the particles are arranged in a capillary or in a micro fluid channel chip (Nucleic Acids Research 30, e87 (2002); Japanese Patent No. 3593525; and Japanese Patent Application Publication No. 2005-17224) is adopted.
For the conventional DNA chip or protein chip, for quantitative analysis of plural types of probes contained in a test sample, the reaction with the oligomers or the DNA or protein probes immobilized on the chip is allowed to occur, which takes from half a day to a day. On the other hand, for the probe array in which the particles are arranged in the capillary (Nucleic Acids Research 30 e87 (2002)), namely, the particle array, the test sample is forced to flow into and through the capillary. Since the particle array is more likely to enable a reduction in gene testing time as compared to the conventional method, it is measuring technology capable of not only being used in a relatively large-scale clinical test center but also being used for in-hospital or on-the-spot summary measurement, namely, Point of Care Testing (POCT). For example, the particle array can be expected to come into use as a means for quickly detecting a foreign gene that does not exist in a pathogenic microbe genome in itself, for an infection or bacteria test or the like for which a prompt diagnosis is urgently required.
For practical use of the particle array adopting the method that involves identifying the type of probe by the sequence in which the particles are arranged in the capillary (Nucleic Acids Research 30, e87 (2002)), the establishment of a method for selecting any given probe-immobilized particle in accordance with what purpose a test is used for and thereby arraying the particles as desired is essential, and thus, there have been proposals of several methods. For example, the methods include a method that involves effecting the flowing of the particles into the capillary, utilizing the flow of liquid, while performing individual control of the particles one by one (Japanese Patent Application Publication No. Hei 11-243997), and a method in which only one particle selected from among plural particles introduced in conjunction with a solvent is held on a sheet having formed therein a microscopic hole that admits only one particle, and the sheet is moved, with the particle held thereon, to the position of a channel formed in any one of the capillary and a flat sheet, whereby the particles are arranged (Japanese Patent Application Publication No. 2000-346842). However, these methods have a problem with reliability or usability because of often taking in the particles unsuccessfully under the influence of air bubbles.
Therefore, there has been a proposal of a method that involves using a particle capturing nozzle to capture, and manipulate, only one particle on its tip suction unit from within a container stocked with plural particles having probes of one and the same type immobilized thereon in conjunction with a solution (Japanese Patent No. 3593525; Japanese Patent Application Publication No. 2005-17224; and Analytical Chemistry 75, 3250-3255 (2003)). This method enables arraying the particles in intended sequence.    Patent Literature 1: Description in U.S. Pat. No. 6,023,540    Patent Literature 2: Japanese Patent Application Publication No. Hei 11-243997    Patent Literature 3: Japanese Patent Application Publication No. 2000-346842    Patent Literature 4: Japanese Patent No. 3593525    Patent Literature 5: Japanese Patent Application Publication No. 2005-17224    Non-patent Literature 1: Science 251, 767-773 (1991)    Non-patent Literature 2: Science 270, 467-470 (1995)    Non-patent Literature 3: Nat. Biotechnol. 18, 438-441 (2000)    Non-patent Literature 4: Clinical Chemistry 43, 1749-1756 (1997)    Non-patent Literature 5: Nucleic Acids Research 30, e87 (2002)    Non-patent Literature 6: Analytical Chemistry 75, 3250-3255 (2003)